Diseases of the Bone Flashcards
Outline the process of vitamin D synthesis.
- 7-dehydrocholesterol + UVB -> Cholecalciferol (pre-VitD) -> WAT (storage) or Liver (activation)
- Cholecalciferol + 25alpha-hydroxylase (CYP2R1) -> 25-hydroxycholecalciferol (Liver)
- 25-hydroxycholecalciferol + 1alpha-hydroxylase (CYP27B1) -> Calcitriol (Kidneys)
Calcitriol ≈ increased Calcium resorption + inhibits PTH secretion
What is the precursor to vitamin D?
7-Dehydrocholesterol
What is the catalyst for production of cholecalciferol?
UVB
What converts cholecalciferol to 25-hydroxycholecalciferol?
25-a-OHase
What converts 25-hydroxycholecalciferol to Calcitriol?
1-a-OHase
What is the site of production of 25-hydroxycholecalciferol?
Liver
What is the site of production of Calcitriol?
Kidneys
What is Osteoporosis?
Bone disease caused by reduction in bone mass and micro-architectural deterioration of bone tissue leading to fragility and increased fracture risk
Give the definition for osteopenia
- Osteopenia: 2.5 SD – 1 SD
Give the definition for osteoporosis
- Osteoporosis: ≥ - 2.5 SDs
Give the Tx for OP
• Bisphosphonates: Alendronate/ Risedronate/ Zoledronate
-> inhibit bone resorption
• SERMs: Raloxifene
-> Spinal Fx reduction
± (Intolerance to 1st and 2nd line/ Pregnancy)
• Denosumab
-> RANKL inhibitor
-> Indicated in pregnancy
± (Post-menopausal)
• HRT: Oestrogen
± (Hypogonadism)
• HRT: Testosterone
76 year old female presents with a recent NOF Fx.
Her DEXA score is < 2.5 SDs and she has a significant kyphosis.
Give your Dx and Tx
Osteoporosis
• Bisphosphonates: Alendronate/ Risedronate/ Zoledronate
-> inhibit bone resorption
• SERMs: Raloxifene
-> Spinal Fx reduction
± (Intolerance to 1st and 2nd line/ Pregnancy)
• Denosumab
-> RANKL inhibitor
-> Indicated in pregnancy
± (Post-menopausal)
• HRT: Oestrogen
± (Hypogonadism)
• HRT: Testosterone
What assessment tool may be used for fracture risk?
FRAX
What is osteoporosis?
Condition caused by reduced bone resorption by osteoclasts leading to craniofacial abnormalities, chest wall deformities and skeletal enlargement
A 34 year old Afrikaaner presents with a numbness and inability to move muscles in his face. He also reports some recent hearing loss.
O/E he has macrognathia, hearing loss and a facial nerve paralysis.
A DEXA shows increased BMD of calvarial bone and the appendicular skeleton.
Give your DDx and Tx
Osteoporosis
Symptomatic management
What is Osteomalacia?
Disease of the bone due to vitamin D deficiency causing hypomineralisation of the osteoid framework leading to soft bones in children (Rickets) and adults (Osteomalacia) characterised by proximal muscle weakness, bone deformities (genu valgus and bowing) and impaired growth
A 10 year old presents with bowing and muscle weakness. His shoulder muscles have recently become less powerful.
O/E you note genu valgum and tibial bowing. Additionally his SCM and Trapezius power is 3/5.
An XR shows Looser’s psuedofractures and defective mineralisation.
Give your DDx and Tx.
Rickets / Osteomalacia
• Vitamin replacement: 25-hydroxyvitamin D at 50 000U for 8/52
What is Paget’s disease?
Bone disorder caused by aberrant remodeling featuring osteoclast resorption and deficient osteoblast deposition resulting in new, weaker bone, hyperperfusion in bone and fibrous tissue
A 67 year old male presents with bone pain and hearing loss. He has a PMHx of asthma which is well controlled, drinks 12 units a week and has a pack years of 10 years.
O/E you notice hearing loss on the R side, bone pain which is diffuse
His ALP is raised, but Calcium is normal as is Phosphate. An XR shows bone enlargement, sclerotic changes and osteolytic areas.
Give your DDx and Tx
Paget’s disease of the bone
• Bisphosphonates: Zoledronate
What is osteonecrosis?
Bone disease causing death of bone and marrow cells due to hypoperfusion
Give 5 cause of Osteonecrosis.
- Drugs: Glucocorticoids/ Bisphosphonates
- Sickle cell disease
- Trauma
- Radiation
- HIV infection
What is Hyperparathyroidism?
Endocrine cause of bone disease featuring excessive secretion of parathyroid hormone (PTH) from the parathyroid gland which can be categorized into primary, secondary or tertiary dependent on biochemical abnormalities and aetiology.
What is Primary Hyperparathyroidism caused by?
Hyperactive PT gland = RANKL secreted to RANK on Oc = activation
What is secondary Hyperparathyroidism caused by?
Low calcium feedsback to PT gland -> PTH elevated, Ca2+ low, Pi normal and ALP may be elevated
What is tertiary Hyperparathyroidism caused by?
Untreated secondary hyperparathyroidism causes chronic elevated PTH, elevated Ca2+ and elevated Pi and ALP
What is malignant Hyperparathyroidism caused by?
PTH-rp produced by squamous cell lung carcinoma and renal cell carcinoma
A patient complains of fatigue, malaise and abdominal pain. Their biochemical analysis shows elevated calcium, elevated PTH and elevated ALP.
Give your DDx and Tx
Primary hyperparathyroidism
• Conservative: Fluid intake (reduce calculi)
+
• Cinacalet
-> increase sensitivity of PTH cells to calcium
-> SE: myalgia; low T
± (Duodenal ulcer)
• PPI: Omeprazole
A patient complains of fatigue and malaise and bowing of the limbs. His biochemical derangement shows low calcium, elevated PTH, normal Pi and normal ALP.
Give your DDx and Tx.
Secondary hyperparathyroidism
• Tx underlying condition \+ • Hyperphosphatemia: Binders/ Diet \+ • Vitamin D intake
A patient complains of fatigue and malaise, bowing of the long bones and abdominal pain.
His biochemical derangements show elevated Calcium, elevated PTH, elevated Pi and elevated ALP.
Give your DDx and Tx
Tertiary hyperparathyroidism
3º • Surgery \+ • Hyperphosphatemia: Binders/ Diet \+ • Vitamin D intake
